Date of Completion

2025

Document Type

Thesis

Degree Name

Bachelor of Science in Pharmacy

Keywords

Ylang-ylang (Cananga odorata), antimicrobial resistance (AMR), multidrug-resistant tuberculosis (MDR-TB), Mycobacterium tuberculosis (M. tb.)

Abstract

The escalating burden of antimicrobial resistance (AMR), particularly in multidrug-resistant tuberculosis (MDR-TB), underscores the urgent need for novel and safer therapeutic agents. Given that bacterial DNA gyrase is a well-established target in Mycobacterium tuberculosis (M. tb.), this study aims to identify potential inhibitors of its B subunit (PDB ID: 3ZM7) through computational analysis of phytochemical compounds derived from Ylang-ylang (Cananga odorata). A total of 194 compounds, collected from published databases, were evaluated against the DNA gyrase B subunit of M. tb. through molecular docking simulations that presented binding affinities ranging from -5.6 to -9.3 kcal/mol. β-Amyrin, Betunal, ε-Cadinene, and 5-indanol merged as notable candidates, demonstrating favorable interactions within the ATP-binding pocket of the target enzyme. Through arbitrary inclusion criteria and multi-docking validation, β-Amyrin exhibited the highest binding affinity and strong van der Waals interactions. Molecular dynamics simulations revealed that β-Amyrin maintained a stable binding conformation over time, indicating minimal structural deviations, limited fluctuations at key residues, and strong interaction stability. In comparison to the standard Novobiocin, β-Amyrin showed a great performance in parameters related to interaction stability and binding consistency, whereas Novobiocin was revealed to have a good structural stability and strong binding affinity due to its extensive hydrogen bonding. In contrast, 5-indanol stood out for its comparatively better pharmacokinetic properties despite lower binding energy and predicted toxicity, suggesting modification of the compound. β-Amyrin, along with 5-indanol, demonstrates favorable binding behavior and interaction stability, positioning it as a promising lead compound for further modification. The in silico-driven framework and predicted toxicity enable early-stage identification of novel anti-TB candidates and highlight the therapeutic potential of Ylang-ylang (Cananga odorata) in addressing MDR-TB through structure-based drug design.

First Advisor

Rhenz Alfred D. Liman, RPh, MS

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